Voltammetric determination of Imatinib (Gleevec) and its main metabolite using square-wave and adsorptive stripping square-wave techniques in urine samples

The voltammetric behaviour of Imatinib (STI 571) and its main metabolite (N-demethylated piperazine derivative) were studied by square-wave techniques, resulting in to two methods for their determination in aqueous and urine samples at pH 2. The application of the square-wave (SW) without the adsorptive accumulation and voltammetric stripping (AdSV) exhibit a peak at a reduction potential of -0.70V for an accumulation potential of -0.45 V. The sensitivity was higher for the stripping technique because a signal four times higher than that provided by the square-wave method without the previous accumulation was obtained. Due to the fact that Imatinib and its metabolite show the same voltarnmetric reduction process, some experiments were performed in order to compare the voltarnmetric response of Imatinib and its main metabolite in a similar ratio than that of the therapeutic concentration. The calibration curve for Imatinib in urine was linear in the range from 1.9 x 10(-8) to 1.9 x 10(-6) M in stripping mode with an accumulation time (t(acc)) of 10s. The relative standard deviations obtained for concentration levels of Imatinib as low as 2.0 x 10(-7) M for square-wave was 2.17 % (n = 9) and for stripping square-wave was 2.65 % (n = 9) in the same day. The limits of detection for square-wave and stripping square-wave were 5.55 x 10(-9) and 5.19 x 10(-9) M, respectively. Thus, the presented method are straightforward, rapid and sensitive and has been applied to the determination of Imatinib and its main metabolite altogether in urine samples from real patients. (c) 2004 Elsevier B.V. All rights reserved.